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CD24 promoted cancer cell angiogenesis via Hsp90-mediated STAT3/VEGF signaling pathway in colorectal cancer
- Source :
- Oncotarget
- Publication Year :
- 2015
-
Abstract
- CD24 is involved in tumor progression of various cancers, but the effects of CD24 on tumor angiogenesis in colorectal cancer are still unknown. We aimed to investigate the underlying mechanism and role of CD24 on colorectal cancer (CRC) angiogenesis. Our data showed that the microvessal density (MVD) was related to the expression of CD24 in primary and metastasis CRC. Silencing of CD24 could dramatically decrease human umbilical vein endothelial cell (HUVEC) migration, invasion and tubule formation, but trivially affected cell proliferation. We also mechanically showed that silencing CD24 could downregulate the expression of VEGF via inhibiting the phosphorylation and translocation of STAT3. Moreover, Hsp90 was identified as the down-interaction protein of CD24 with co-immunoprecipitation assay and systematic mass spectrometry. Immunofluorescence results showed Hsp90 partly co-localized with CD24 in CRC cell membrane and there was a positive correlation between CD24 and Hsp90 expression in CRC tissues. We gradually evidenced that Hsp90 modulated the stability and degradation of CD24 in a proteasome-depended manner, and transferred the signal transmission from CD24 to STAT3. 17-AAG, a specific Hsp90, could abrogate the CD24 induce- HUVEC migration, invasion and tubule formation in vitro and in vivo. Collectively, our results suggested that CD24 induced CRC angiogenesis in Hsp90-dependent manner and activated STAT3-mediated transcription of VEGF. We provided a new insight into the regulation mechanism of tumor angiogenesis by exploring the role of CD24 in angiogenesis.
- Subjects :
- 0301 basic medicine
STAT3 Transcription Factor
Vascular Endothelial Growth Factor A
Angiogenesis
Hsp90
colorectal cancer
Chick Embryo
Metastasis
03 medical and health sciences
Mice
angiogenesis
0302 clinical medicine
Membrane Microdomains
Cell Line, Tumor
VEGF Signaling Pathway
Medicine
Animals
Humans
HSP90 Heat-Shock Proteins
skin and connective tissue diseases
CD24
Neovascularization, Pathologic
business.industry
Cell growth
CD24 Antigen
medicine.disease
VEGF
Vascular endothelial growth factor A
030104 developmental biology
Oncology
Tumor progression
030220 oncology & carcinogenesis
Immunology
Cancer cell
Cancer research
Human umbilical vein endothelial cell
business
Colorectal Neoplasms
Signal Transduction
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 7
- Issue :
- 34
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....e0160adfd7efcc93efdfddb817a6f12f